During sexual behavior, copulation related sensory information and modulatory signals from the brain must be integrated and converted into the motor and secretory outputs that characterize ejaculation (Lenschow and Lima, Current Opinion in Neurobiology, 2020). Studies in humans and rats suggest the existence of interneurons in the lumbar spinal cord that mediates that step: the spinal ejaculation generator (SEG). My work aimed at gaining mechanistic insights about the neuronal circuits controlling ejaculation thereby applying cutting-edge techniques. More specifically, we mapped anatomically and functionally the spinal circuit for ejaculation starting from the main muscle being involved in sperm expulsion: the bulbospongiosus muscle (BSM). Combining viral tracing strategies with electrophysiology, we specifically show that the BSM motoneurons receive direct synaptic input from a group of interneurons located in between lumbar segment 2 and 3 and expressing the peptide galanin. Electrically and optogenetically activating the galanin positive cells (the SEG) lead to the activation of the motoneurons innervating the BSM and the muscle itself. Finally, inhibition of SEG cells using DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) in sexual behaving animals is currently conducted to reveal whether ejaculation can be prevented.

Many microorganisms and cells function in complex (non-Newtonian) fluids, which are mixtures of different materials and exhibit both viscous and elastic stresses. For example, mammalian sperm swim through cervical mucus on their journey through the female reproductive tract, and they must penetrate the viscoelastic gel outside the ovum to fertilize. In micro-scale swimming the dynamics emerge from the coupled interactions between the complex rheology of the surrounding media and the passive and active body dynamics of the swimmer. We use computational models of swimmers in viscoelastic fluids to investigate and provide mechanistic explanations for emergent swimming behaviors. I will discuss how flexible filaments (such as flagella) can store energy from a viscoelastic fluid to gain stroke boosts due to fluid elasticity. I will also describe 3D simulations of model organisms such as C. Reinhardtii and mammalian sperm, where we use experimentally measured stroke data to separate naturally coupled stroke and fluid effects. We explore why strokes that are adapted to Newtonian fluid environments might not do well in viscoelastic environments.

The journey of development begins with sperm swimming through the female reproductive tract en-route to the egg. In order to successfully complete this journey sperm must beat a single flagellum, propelling themselves through a wide range of fluids, from liquified semen to viscous cervical mucus. It is well-known that the beating tail is driven by an array of 9 microtubule doublets surrounding a central pair, with interconnecting dynein motors generating shear forces and driving elastic wave propagation. Despite this knowledge, the exact mechanism by which coordination of these motors drives oscillating waves along the flagellum remains unknown; hypothesised mechanisms include curvature control, sliding control, and geometric clutch. In this talk we will discuss the mechanisms of flagellar bending, and present a simple model of active curvature that is able to produce many of the various sperm waveforms that are seen experimentally, including those in low and high viscosity fluids and after a cell has ‘hyperactivated’ (a chemical process thought to be key for fertilization). We will show comparisons between these simulated waveforms and sperm that have been experimentally tracked, and discuss methods for fitting simulated mechanistic parameters to these real cells.

Microorganisms can swim in a variety of environments, interacting with chemicals and other proteins in the fluid. In this talk, we will highlight recent computational methods and results for swimming efficiency and hydrodynamic interactions of swimmers in different fluid environments. Sperm are modeled via a centerline representation where forces are solved for using elastic rod theory. The method of regularized Stokeslets is used to solve the fluid-structure interaction where emergent swimming speeds can be compared to asymptotic analysis. In the case of fluids with extra proteins or cells that may act as friction, swimming speeds may be enhanced, and attraction may not occur. We will also highlight how parameter estimation techniques can be utilized to infer fluid and/or swimmer properties.

In the 17th century, Antonie van Leeuwenhoek used one of the earliest microscopes to see how sperm swim. He described the sperm as a “living animalcule” with a “tail, which, when swimming, lashes with a snakelike movement, like eels in water”. Strikingly, this perception of how sperm moves has not changed since. Indeed, anyone today with a modern microscope would make the same observation: sperm swim forward by wiggling their tail symmetrically side-to-side. Our new research using 3D microscopy shows that we have all been victims of a sperm deception, an illusion. Only now we can see that for 350 years we have been wrong about how sperm actually swims.